The proposed studies are designed to define the physiology and significance of glucagon secretion and action and to gain insight into hormonal control of carbohydrate and intermediary metabolism, particularly as they relate to the fetus, newborn and child. The significance of glucagon secretion in utero will be explored in the fetal lamb preparation utilizing somatostatin (SRIF), an inhibitor of insulin and glucagon secretion, SRIF will be infused alone or in conjunction with physiologic replacement of either hormone. Mechanisms responsible for the surge in neonatal glucagon which occurs after umbilical cord cutting, will be explored through the use of SRIF, adrenergic agonists and antagonists, prostaglandin antagonists (indomethacin aspirin) and provision of intravenous nutrients. The significance of this glucagon surge will be defined in newborn lambs through the use of SRIF, and the maturation and induction of the hepatic glucagon receptor will be defined using fetal and newborn rats from normal or diabetic (streptozotocin) mothers. Further characterization of the significance of glucagon in human newborns will be sought in infants of diabetic mothers where glucagon secretion is deficient, and the effects of glucagon on glucose turnover and gluconeogenesis from alanine in these and normal infants will be explored using micro-techniques and non-radioactive, isotopic labels. The secretion, suppressibility and role of glucagon in the pathogenesis and maintenance of diabetes mellitus will be explored in various "genetic" forms of diabets, and the potential role of SRIF as an adjunct to therapy in juvenile diabetes will be investigated. These studies are made possible through established methodology for the measurement of glucagon, insulin, growth hormone, cortisol, prostaglandins, glucose, ketone bodies and fatty acids, and by the availability of established animal models and clinical material. The studies should extend knowledge of carbohydrate energy homeostasis and its neurohumoral control, and may provide newer insights for the rational treatment of hypoglycema and diabetes mellitus; major diseases in pediatrics.